Journal Club: What is a Stem Cell?

This is a new writing exercise in which I'll post about an article that was discussed in my lab's journal club. Recently, we read a new paper by some preeminent figures in the stem cell field.

The paper, No Identical ‘‘Mesenchymal Stem Cells’’ at Different Times and Sites: Human Committed Progenitors of Distinct Origin and Differentiation Potential Are Incorporated as Adventitial Cells in Microvessels, was published in June 2016, in the journal Stem Cell Reports. The full text of this open access paper is available here.

A new paper by Benedetto Sacchetti, part of recently deceased Paulo Bianco's research group, seeks to clarify some much needed points in the world of mesenchymal stem cells or MSCs, and their lack of universally accepted definitions. In fact, the authors also argue against using the term “MSC,” as it is misleading. They claim that stem cells should be named by their tissue of origin instead, because as shown, these cells retain characteristics of where they were isolated from, despite sharing some similarities.

An increasing number of stem cell clinics are popping up, claiming everything from anti-aging benefits to curing diseases. These clinics are pulling *something* out of people, calling this random slurry "stem cells," and injecting it back into clients. This is a false and dangerous practice. While stem cells have great therapeutic potential, there is still much work to be done in basic research before these claims can be verified or even tested. This issue is further complicated by some people in the stem cell field that claim “MSCs” can cure everything from stroke to osteoarthritis. While some of the research is promising, there is no clear definition of an “MSC," let alone well documented therapies.

In Sacchetti's paper, they clearly show that stem cells from different tissues have different abilities to differentiate, and are not ubiquitous, despite having some similar characteristics. The authors look at cells from four different tissues: bone marrow, muscle, the outer surface of bone, and umbilical cord blood. 

Currently, stem cells are isolated for research using proteins that sit on the surface of the cell. This paper shows that despite having similar surface markers, cells from different tissues have clearly distinct gene expression patterns, shown with two different clustering techniques. Each of the four types of stem cell retain a gene expression pattern that is directly related to their respective tissue of origin. 

Next, this paper explores the differentiation ability of stem cells from different origins. Only the cells from bone marrow or periosteum (also a bone-related tissue), were able to form new bone, complete with bone marrow inside. Cells from muscle did not make bone, and cells from cord blood weren't able to form complete bone marrow. The ability of a cell to make new bone, including bone marrow is a defining marker of a skeletal stem cell. 

Following this, they looked at the ability of these four types of stem cells to differentiate into muscle. As before, only the cells that were isolated from muscle retained the ability to differentiate into muscle, while the other three were not. This was also shown by looking at the ability of these cells to regenerate muscle after an injury, and again only the muscle derived cells were able to make new muscle. 

The overarching point of this paper is that cells from different tissues shouldn’t be uniformly referred to as “MSCs”, when they clearly show differences. Instead, they should be referred to by their tissue of origin. While there are some similarities, the inherent ability of each cell type to differentiate is different. 

Keep moving

Some people, (I have a specific former intern in mind) are scared to move forward. They don't know what to do. They may be working on an undergraduate degree and not getting the grades they want, because they know their studying technique isn't very good. Or maybe stuck in a job they don't like because they don't know what they want to do with their life.

I ask them for ideas, brainstorms. What do you want your life to look like? What classes do you do really well in? Why are those different? What things could happen today to make it a wonderful day?

They can often answer these questions, but don't know the next step. They're scared of doing something wrong, or worse, trying and then failing.

Seeing this multiple times and listening to people further along in their career than I have lead to the same conclusion.

Success is not the opposite of failure, it's the step after it.

Too many people I know are scared of failure. I want to say to them, "Failing is okay!" Failure happens. You can survive failure. It's lack of motion, lack of action that will kill you. It doesn't matter if the action you choose doesn't work the way you want it to. Once you start moving forward, you can more easily evaluate your position, and make changes to it. It's getting that first step that's the hard part.

I told my intern that was struggling with his grades, that it doesn't really matter what study habits he tries to change. The point is to change something, and see if it works. It may not. It probably won't. But he will  have tried something, he can check it off the list if it doesn't work and then try something else. He will eventually find a study method that works really well for him, and more importantly, learn which ones are a waste of his time.

A mentor said something that really stuck me: "It's like riding a bike, you need forward momentum before you can change direction." So get moving, fall a few times, fail a few times, and keep going.

2015 in Review & Looking Forward

At the end of 2014 I wrote a post about my goals for 2015, and revisited them  halfway through the year. Which did I accomplish and which will I carry to 2016?

Professional:

• Publish in a policy journal again - Sure didn't, although I did publish a first author research paper, and started writing a second one. I have some ideas for a policy paper, but need to make it a priority if I want it to actually happen. Research papers are a much higher priority, so this is a maybe for 2016.
• Plan & execute DC networking trip - I did a lot of networking this year, and met some really awesome people. My long term career goals have changed, so this is now off the list.
• Identify & explore specific science policy careers - I'm leaning more towards staying in academia and research labs, where I can still read, write, and think about policy issues. I still plan on exploring career options as the opportunities arise.
• Find session/panel to moderate at future conference - I found the professional society I want to be most involved in (American Society for Bone and Mineral Research), and am exploring how to do so in 2016.
• Finish strategic outreach plan for CCH - Done! Interesting side project, glad it's over.
• Co-moderate PhD Career Conference 2015 - Done! This was fun, stressful, and a great learning opportunity. I got to interact with all of the fantastic alumni we brought in. Now I have to decide if I want to help coordinate it again in 2017.
• New goal: Mentoring - We have new people starting in the lab this year. Rotation students, undergrads, and likely a new technician at some point. I enjoy mentoring and helping new people, and would like to continue to develop this skill. 
• New goal: Say no - I did a lot this year in terms of running student groups, moderating workshops, and volunteering. Most of it was fun, and I learned something from all of it. However, it was a lot to take on and I feel like my attention was never fully on any one thing. This year, I'm going to try the Derek Sivers approach of Hell Yeah or No. Unless it's something I'm super excited about, I'm going to pass. (Caveat: Considering my general enthusiasm for most things in life, this may not free up as much time as I hope...)

School:

• Submit F31 grant - Done! Submitted in December, which is a later deadline than originally intended, but it was a better grant this way. Now that I've struggled through this process once, I want to do it again. I'm hoping to be more involved in my PI's next few submissions, in addition to finding more grant writing opportunities for myself.
• Pass qualifying exam - DONE! The lead up was without a doubt the most chronic stress I've ever experienced. The exam itself was fun, in a weird way. I may write a more extensive post about this in the future.  
• Attend 2 conferences - Done! I actually went to three conferences in 2015, winning one poster award and two travel grants. I've been to enough conferences at this point that I'm going to be a little pickier about which I attend in the future. ASBMR is a definite, and I'd like to attend a Gordon Conference at some point as well.
• First author scientific paper - Done! Submitted, accepted, and already writing the next one.
• Read at least 1 paper per week - Not quite. I've been scanning more abstracts, but need to focus on more indepth reading. One of my goals for 2016 is to start blogging about our biweekly journal club. One comment from my qualifying exam is that I need to be more familiar with the literature. 
• New goal: Push my own research forward. My most recent papers were from finishing projects that had started in the lab before I joined. Now that I'm generating a decent amount of my own data, I need a broad outline of what needs to be done before this can be written up.

There are also a number of personal and fitness goals for 2016, but those are currently in flux, and don't seem as interesting to blog about. How was your 2015? What goals have you set for 2016?

Quals incoming!

My qualifying exam is coming up, in a little over a month and a half.

The format is writing the research strategy of an R01, based on proposed research for the next few years, then presenting and defending the ideas to your committee. I've been working on mine almost daily since May, and it's changed dramatically as the direction of my project has shifted. It's been fun, interesting, challenging, and utterly terrifying.

Other students I talk to say this was one of the worst parts of their PhD, the lead up to quals. These same people say that in retrospect, it wasn't that bad, and they enjoyed the actual event, in a twisted sort of way.

I've been trying to get the last few bits of preliminary data, and it's not going well. I would have no problem with data that contradicted my hypothesis, if only the experiments would work. That frustration aside, the writing process has been enlightening. Reading papers, and putting this puzzle together has been satisfying in a way I hadn't expected. I don't mind the writing at all, but I'm dreading the studying that I should have already started. I'm also looking forward to dedicated time in the lab again, instead of random hail mary experiments.


How was your qualifying exam? Horrible? Wonderful? What do you wish you had done differently?

Onwards, and forwards!

Halfway Done! Revisiting 2015 Goals

June. It's June already. Where did 2015 go? Time is flying by at a ridiculous pace. In January I wrote a post about goals I wanted to achieve for 2015. Since 2015 is halfway over, let's revisit.

Professional:

• Publish in a policy journal again - Not even close, and maybe not something I want to focus on.
• Plan & execute DC networking trip - Went to DC, but not for this purpose. still managed to get some networking in.
• Identify & explore specific science policy careers - This is still a struggle
• Find session/panel to moderate at future conference - I'm going to a conference in October where I may look for future opportunities.
• Finish strategic outreach plan for CCH - Done! Interesting side project, glad it's over.
• Co-moderate PhD Career Conference 2015 - Currently in the final stages of setting up workshops, this event is at the end of June.

School:

• Submit F31 grant - Still writing, writing, writing. Submission deadline is in August.
• Pass qualifying exam - Committee is formed, this will be scheduled for September.
• Attend 2 conferences - Done! Going to a 3rd in October.
• First author scientific paper - Done! Submitted earlier this week, keep your fingers crossed that comments are kind, and revisions are light.
• Read at least 1 paper per week - Not quite. I've been scanning more abstracts, but need to focus on more indepth reading.

Fitness:

• 300lb deadlift - Not even close
• Gym at least 2x/week - Only for the last month or so. As this continues more of the other goals in this category will seem more attainable.
• 10 sec L-sit
• Freestanding handstand
• 5 pull-ups
  

Personal:

• Travel out of the country - Twice! Once for a conference, and once for fun.
• Complete Linux online course - Nope. This isn't a goal any more.
• Practice piano 3x/week - I don't think I've looked at my keyboard since January.
• Take singing/piano lessons - No longer a goal, but I might take lessons after I pass my Quals.
• Blog monthly - Obviously this hasn't been happening.
• Have more science-specific Twitter discussions - This has been happening periodically, and it's always enjoyable. 

Looking over the list, I'm pretty okay with my progress so far. Some goals have changed, and that's acceptable. I specifically didn't add goals to this list, but priorities have definitely shifted to focus on personal fitness, and my research project. In January, I was still in classes, and focusing on bigger picture, career orientated goals instead. This mid-year shift seems appropriate, and we'll have to see what I think looking back at the end of this year!

How are your goals coming along?